Heat Stress Produces Lasting Cellular Resilience via Formation of Tetraspanin Webs

In this study, we use a robust thermal stress paradigm in C. elegans to uncover causal mechanisms by which transient stress may exert lasting impacts on organismal resilience and longevity. We show that transient heat exposure at 28°C during late larval development activates the gene tsp-1, which encodes a C. elegans homolog of the evolutionarily conserved tetraspanin protein family. Tetraspanin 1 (TSP-1) proteins form tetraspanin web-like structures and are essential for maintaining membrane permeability, barrier functions, and heat-induced organismal resilience and longevity. Initial induction of tsp-1 by heat requires the histone acetyltransferase CBP/p300 homolog (CPB-1); however, unexpectedly, this results in sustained up-regulation of TSP-1 protein without a corresponding increase in mRNA abundance. Our data suggest that tsp-1 expression leads to TSP-1 protein multimerization and the formation of stable tetraspanin web structures, which persist even in the absence of initial stimuli and tsp-1 transcript up-regulation. This tetraspanin web-based stable protein structure formation represents an intriguing mechanism of cellular memory, distinct from previously known modes of epigenetic regulation primarily occurring in the nucleus, such as DNA and histone modifications.
Source: Fight Aging! - Category: Research Authors: Tags: Medicine, Biotech, Research Source Type: blogs